Self-signal Amplifying Molecular Biosensor ::
The Detection of Potentially Harmful Agents at a Cellular Level

By Bill Clayton

IN 2003, A YOUNG woman underwent routine mammography during an annual checkup. Thirty minutes later, she and an oncologist were planning a treatment for breast cancer. Fortunately, early detection made the cancer much easier to treat - today the woman is a healthy survivor. But many others aren't so fortunate. It would be monumentally helpful if doctors had the technology to examine the molecular dynamics of cells and identify aberrations long before cancer and other life-threatening diseases could develop.

Assistant Professor Jinsang Kim has been pursuing just such technology. "Sensing any defects in a DNA sequence or abnormally high levels of a particular protein at the molecular level can accelerate the discovery of abnormal cells by locating them very early in development," Kim said. "So we're investigating a self-signal amplifying molecular biosensor. The idea behind it is to combine the signal-amplifying property of conjugated polymers and the fact that various biological molecules have very specific characteristics."

Polymer DNA and only dye-labeled DNA were excited at the wavelength of 365 nm, creating differing emission spectra.
(Inset: A solution containing conjugated polymers generates fluorescent light.)

Conjugated polymers are a relatively new class of materials that can be designed to have their own unique properties and abilities - for example, they can conduct electricity and generate fluorescent light. One of their attractive applications is in sensor design, because any change around just one segment of the conjugated polymer chain can affect the properties of the entire chain, producing large signal amplification. This amplification is directly proportional to the intensity of light that the chain emits.

"Sensitivity and the ability to detect a target molecule selectively are the most important parameters of a sensor," Kim said. "Fortunately, nature is very precise - that is, its processes provide very accurate results that we can read and interpret. In biosynthesis, both the information transfer from DNA to RNA and the synthesis of proteins according to the information carried on the messenger RNA are highly accurate signatures. And the enzymes - the proteins that act as biochemical catalysts - are also very specific in their functions. The specificity of bio-systems, when combined with unique signal-amplification properties of various synthetic conjugated polymers, can give us the ability to design best performing sensors."

To create this optimal sensor, researchers bio-conjugate a specific DNA or protein sequence to form a hybrid polymer that can detect a specific biological molecule and, in response, generate and amplify a sensitive fluorescent signal.

Kim, who's associated with the departments of Materials Science and Engineering, Chemical Engineering, and Biomedical Engineering, and the Macromolecular Science and Engineering program, anticipates that in the near future these highly sensitive and accurate biosensors will enable doctors to screen gene-related diseases in their early stages. Also, because the most reliable way to identify a virus or microbe is to pinpoint its genetic code, these biosensors have the potential to strengthen national security by detecting organisms that could endanger food and water supplies.

The far-reaching applications of these molecular biosensors are impossible to foresee. But it's certain that they'll become powerful life-saving tools in the future. -E

Program supported by the NSF.